This RSDA renewal application is to support the career development of Dr. William Woolverton as research scientist in drug abuse. The candidate has a 25-year history of drug abuse research and has been funded continuously by NIDA for the past 14 years. His primary area of research is drug self administration with nonhuman primates as subjects. This model has played a central role in developing our understanding of drug taking. The PI proposes to extend this model using novel approaches to examine in detail the neurobiological and behavioral mechanisms that control drug taking by non-human primates, and, by extension, humans. Pharmacological studies consistently suggest the importance of CNS dopamine (DA) mechanisms in cocaine abuse. However, interpretation of those studies is ambiguous and the quantitative relationship between pharmacological mechanisms and reinforcing effect has not been established. The proposed research will examine that relationship by testing the hypothesis that relative intrinsic efficacy of a DA agonist determines its relative efficacy as a positive reinforcer. These studies will use agonists and antagonists for DA receptors and transporters ans correlate in vivo findings with in vitro results in rhesus monkey brain tissue. Behavioral mechanisms control drug abuse, as well. Since drugs are usually available to humans either simultaneously or sequentially with other reinforcers, an understanding of factors that control choice between drugs and other drug or non-drug reinforcers is important to a complete understanding drug abuse. The experiments described in the present proposal will examine the applicability to drug choice of models of choice that have evolved from the experimental analysis of behavior: matching and maximizing. Although these models have been shown to account for substantial amounts of data from experiments utilizing non-drug reinforcers, there has been little or no research designed to establish the generality of there models to drugs as reinforcers. This RSDA will allow the candidate to continue and enhance the development of his career as a drug abuse scientist. The research described in the present application will extend and refine the analysis of neurobiological and behavioral control of drug taking using the non- human primate model. In addition, it will have important implications for understanding basic mechanisms controlling drug abuse, for the development of treatment medications, and suggest behavioral approaches to modifying drug choice.